A Phase I trial assessing the safety and tolerability of a therapeutic DNA vaccination against HPV16 and HPV18 E6/E7 oncogenes after chemoradiation for cervical cancer
Mené sur 10 patientes atteintes d'un cancer du col de l'utérus, cet essai de phase I évalue la toxicité et la tolérabilité de
Purpose : This study assessed the safety and tolerability of therapeutic immunization against the HPV viral oncoproteins E6 and E7 in cervical cancer patients following chemoradiation. Experimental Design : MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is co-injected with an IL-12 plasmid followed by electroporation with the CELLECTRA® 5P device. Two to 4 weeks following chemoradiation, patients with newly diagnosed stage IB1-IVA (Cohort 1) or persistent/recurrent (Cohort 2) cervical cancers were treated with four immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-
γ (IFNγ), ELISA for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. Results
:
10 patients (Cohort 1 n=7; Cohort 2 n=3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all Grade 1, primarily related to the injection site. 8 of 10 patients had detectable cellular and/or humoral immune responses against HPV antigens following chemoradiation and vaccination: 6/10 patients generated anti-HPV antibody responses and 6/10 patients generated IFNγ producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8+ T cells and decreased PD-1+CD8+, PD-L1+CD8+ and PD-L1+CD68+ subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. Conclusions
:
Adjuvant MEDI0457 is safe and well-tolerated after chemoradiation for locally advanced and/or recurrent cervical cancers supporting further investigation into combining tumor-specific vaccines with radiotherapy.
International Journal of Radiation Oncology, Biology, Physics